Emergence of Clinically Macrolide-Unresponsive Mycoplasma pneumoniae Segmental/Lobar Pneumonia and COVID-19 Pneumonia in Children in Taiwan, 2024–2025

<b>Background:</b> To date, no study has compared the clinical characteristics of <i>Mycoplasma pneumoniae</i>-associated segmental/lobar pneumonia, <i>Mycoplasma</i> bronchopneumonia, and COVID-19 pneumonia primarily caused by the NB.1.8.1 variant in children. <b>Methods</b>: We examined the epidemiologic trends of pneumonia, segmental/lobar pneumonia, and COVID-19 pneumonia at a teaching hospital from 2015 to 2025. In addition, we compared the clinical characteristics of children hospitalized with <i>Mycoplasma</i> segmental/lobar pneumonia, <i>Mycoplasma</i> bronchopneumonia, and COVID-19 pneumonia during the NB.1.8.1 variant wave in 2024-2025. <b>Results</b>: Between 2015 and 2024, 10,601 pneumonia cases were identified, including 525 cases of segmental/lobar pneumonia and 162 cases of COVID-19 pneumonia. An outbreak of segmental/lobar <i>M. pneumoniae</i> pneumonia and COVID-19 pneumonia occurred in Taiwan during 2024-2025. Starting in early 2025, monthly <i>Mycoplasma</i> positivity rates among children with segmental/lobar pneumonia and bronchopneumonia exceeded 60%. <i>Mycoplasma</i> pneumonia predominantly affected children aged 6-11 years, whereas COVID-19 pneumonia mainly occurred in those younger than 3 years of age. Fever, cough, and rhinorrhea were the most common symptoms in all groups, limiting clinical differentiation. Children with segmental/lobar <i>Mycoplasma</i> pneumonia were more likely to present with prolonged fever (>5 days), lymphocytopenia, a neutrophil-to-lymphocyte ratio (NLR) ≥ 3, and elevated C-reactive protein (CRP) levels, each of which was strongly associated with macrolide non-response (all <i>p</i> < 0.001). <b>Conclusions:</b> Children with segmental/lobar <i>Mycoplasma</i> pneumonia demonstrated more severe clinical manifestations. Segmental/lobar involvement and inflammatory markers, such as lymphocytopenia, elevated NLR, and increased CRP levels, were associated with macrolide non-response. These indicators may help guide therapeutic decision-making in pediatric <i>M. pneumoniae</i> pneumonia.